High rates of relapse to drug use after prolonged drug-free periods characterize the behavior of experienced heroin and cocaine users, and of people in dietary treatment who attempt to restrict the intake of high-fat palatable food.[unreadable] [unreadable] The behavioral and neurochemical events that contribute to these high rates, however, are not well understood. Relapse can be induced in human subjects and laboratory animals by reexposure to the drug (or food) previously used, reexposure to environmental cues paired with drug (or food) self-administration, and by exposure to environmental stressors. We are using an animal model of relapse, a reinstatement model, to study brain systems and neurotransmitters involved in relapse induced by environmental stressors, conditioned drug (or food) cues and drug (or food) reexposure in rats with a history of heroin, cocaine or palatable high-fat food self-administration. [unreadable] [unreadable] During the last year, we reported several findings. In a study with rats trained to self-administer palatable food, we found that the stress hormone corticotrophin-releasing factor plays a role in stress-induced relapse to food seeking, while the gut hormone peptide YY(3-36) plays a role in relapse induced by acute exposure to the palatable food or to cues previously associated with the intake of this food. In studies on the neuronal mechanisms of relapse to heroin seeking induced by exposure to the drug-associated environment, we found that glutamate and dopamine transmission in the rat nucleus accumbens are involved in this relapse. In studies on the molecular mechanisms underlying the time-dependent increases in responsiveness to cocaine-associated cues after withdrawal from the drug, we found that glutamate transmission in the central amygdala plays a role in this phenomenon.